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Development, whether motor, language, social, or spiritual, is the functional expression of complex brain processes throughout one's life span, the foundations of which are laid in childhood. The effects of cancer, chemotherapy, radiation, and surgical procedures on early brain development have been measured using neuroimaging and developmental assessment tools. We propose that spiritual development may be substantially affected in children with oncological diseases that impact underlying brain processes. By drawing connections between science, spirituality, and medicine, we can better address the spiritual needs of children as they cope with oncological diseases, by mitigating emotional, cognitive, and physical symptoms and improving outcomes.

An influential model of the neural mechanisms of creative thought suggests that creativity is manifested in the joint contributions of the Default Mode Network (DMN; a set of regions in the medial PFC, lateral and medial parietal cortex, and the medial temporal lobes) and the executive networks within the dorsolateral PFC. Several empirical reports have offered support for this model by showing that complex interactions between these brain systems account for individual differences in creative performance. The present study examined whether the engagement of these regions in idea generation is modulated by one's eminence in a creativity-related field. Twenty (n ​= ​20) healthy eminent creators from diverse fields of expertise and a 'smart' comparison group of sixteen (n ​= ​16) age- and education-matched non-eminent thinkers were administered a creative generation task (an adaptation of the Alternative Uses Task) and a control perceptual task, while undergoing functional magnetic resonance imaging (fMRI). The participants' verbal responses were recorded through a noise-canceling microphone and were later coded for fluency and accuracy. Behavioral and fMRI analyses revealed commonalities between groups, but also distinct patterns of activation in default mode and executive brain regions between the eminent and the non-eminent participants during creative thinking. We interpret these findings in the context of the well-documented contributions of these regions in the generation of creative ideas as modulated, in this study, by participants' creative eminence., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Nearly everyone has the ability for creative thought. Yet, certain individuals create works that propel their fields, challenge paradigms, and advance the world. What are the neurobiological factors that might underlie such prominent creative achievement? In this study, we focus on morphometric differences in brain structure between high creative achievers from diverse fields of expertise and a 'smart' comparison group of age-, intelligence-, and education-matched average creative achievers. Participants underwent a high-resolution structural brain imaging scan and completed a series of intelligence, creative thinking, personality, and creative achievement measures. We examined whether high and average creative achievers could be distinguished based on the relationship between morphometric brain measures (cortical area and thickness) and behavioral measures. Although participants' performance on the behavioral measures did not differ between the two groups aside from creative achievement, the relationship between posterior parietal cortex morphometry and creativity, intelligence, and personality measures depended on group membership. These results suggest that extraordinary creativity may be associated with measurable structural brain differences, especially within parietal cortex., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: While obesity has been shown to be a risk factor for Alzheimer's disease, the potential mechanisms underlying this risk may be clarified with better understanding of underlying physiology in obese persons., Objective: To identify patterns of cerebral perfusion abnormality in adults as a function of body mass index (BMI) defined weight categories, including overweight or obese status., Methods: A large psychiatric cohort of 35,442 brain scans across 17,721 adults (mean age 40.8±16.2 years, range 18-94 years) were imaged with SPECT during baseline and concentration scans, the latter done after each participant completed the Connors Continuous Performance Test II. ANOVA was done to identify patterns of perfusion abnormality in this cohort across BMI designations of underweight (BMI < 18.5), normal weight (BMI = 18.5 to 24.9), overweight (BMI 24.9 to 29.9), obesity (BMI≥30), and morbid obesity (BMI≥40). This analysis was done for 128 brain regions quantifying SPECT perfusion using the automated anatomical labeling (AAL) atlas., Results: Across adulthood, higher BMI correlated with decreased perfusion on both resting and concentration brain SPECT scans. These are seen in virtually all brain regions, including those influenced by AD pathology such as the hippocampus., Conclusion: Greater BMI is associated with cerebral perfusion decreases in both resting and concentration SPECT scans across adulthood.

The lengthy debate on the validity of the amyloid hypothesis and the usefulness of amyloid imaging and anti-amyloid therapeutic interventions in dementia continues unabated, even though none of them have been able to convince the medical world of their correctness and clinical value. There are huge financial interests associated with promoting both, but in spite of the large sums of money in their support, no effective anti-amyloid treatments or diagnostic use of amyloid imaging have emerged. There are solid scientific reasons that explain these negative results, and it is time to move forward to other promising options for the benefit of the patients.

Importance: Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials., Objective: To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia., Design, Setting, and Participants: This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017., Main Outcomes and Measures: Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype., Results: Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P = .16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P < .001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P < .001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years., Conclusions and Relevance: Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.

Purpose: The purpose of this study was to characterize the neurophysiological and clinical effects that may result from the neuro emotional technique (NET) in patients with traumatic stress symptoms associated with a cancer-related event. We hypothesized that self-regulatory processing of traumatic memories would be observable as physiological changes in key brain areas after undergoing the NET intervention and that these changes would be associated with improvement of traumatic stress symptoms., Methods: We enrolled 23 participants with a prior cancer diagnosis who expressed a distressing cancer-related memory that was associated with traumatic stress symptoms of at least 6 months in duration. Participants were randomized to either the NET intervention or a waitlist control condition. To evaluate the primary outcome of neurophysiological effects, all participants received functional magnetic resonance imaging (fMRI) during the auditory presentation of both a neutral stimulus and a description of the specific traumatic event. Pre/post-comparisons were performed between the traumatic and neutral condition, within and between groups. Psychological measures included the Impact of Event Scale (IES), State Trait Anxiety Index (STAI), Brief Symptom Inventory (BSI)-18, and Posttraumatic Cognitions Inventory (PTCI)., Results: The initial fMRI scans in both groups showed significant increases in the bilateral parahippocampus and brainstem. After NET, reactivity in the parahippocampus, brainstem, anterior cingulate, and insula was significantly decreased during the traumatic stimulus. Likewise, participants receiving the NET intervention had significant reductions (p < 0.05) compared to the control group in distress as measured by the BSI-18 global severity index, anxiety as measured by the STAI, and traumatic stress as measured by the IES and PTCI., Conclusions: This study is an initial step towards understanding mechanistic features of the NET intervention. Specifically, brain regions involved with traumatic memories and distress such as the brainstem, insula, anterior cingulate gyrus, and parahippocampus had significantly reduced activity after the NET intervention and were associated with clinical improvement of symptoms associated with distressing recollections., Implications for Cancer Survivors: This preliminary study suggests that the NET intervention may be effective at reducing emotional distress in patients who suffer from traumatic stress symptoms associated with a cancer-related event.

Background: Depression and cognitive disorders (CDs) are two common co-morbid afflictions that commonly present with overlapping symptoms., Objective: To evaluate if perfusion neuroimaging with brain SPECT can distinguish persons with depression from those with CDs or both conditions., Methods: Inclusion criteria were DSM-IV defined depression or CDs (Alzheimer's disease, vascular dementia, dementia not otherwise specified, and amnestic disorders not otherwise specified) including persons with both (total n = 4,541; 847 CDs, 3,269 depression, 425 with both). Perfusion differences between the groups were calculated using two-sampled t-tests corrected for multiple comparisons. Diagnostic separation was determined with discriminant analysis. Feature selection revealed predictive regions in delineating depression from CDs and comorbid cases., Results: Persons with CDs had lower cerebral perfusion compared to depression. In co-morbid persons, cerebral hypoperfusion was additive, with regions showing lower regional cerebral blood flow compared to either diagnosis alone. Both baseline and concentration SPECT regions yielded correct classification of 86% and leave one out cross-validation of 83%. AUC analysis for SPECT regions showed 86% accuracy, 80% sensitivity and 75% specificity. Discriminant analysis separated depression and CDs from comorbid cases with correct classification of 90.8% and cross validated accuracy of 88.6%. Area under the curve was 83% with sensitivity of 80% and specificity of 70%. Feature selection identified the most predictive regions in left hippocampus, right insula, cerebellar, and frontal lobe regions., Conclusion: Quantitative perfusion SPECT neuroimaging distinguishes depression from dementia and those with both co-morbidities. Perfusion brain SPECT can be utilized clinically to delineate between these two disorders.

Background: National Football League (NFL) players are exposed to multiple head collisions during their careers. Increasing awareness of the adverse long-term effects of repetitive head trauma has raised substantial concern among players, medical professionals, and the general public., Objective: To determine whether low perfusion in specific brain regions on neuroimaging can accurately separate professional football players from healthy controls., Method: A cohort of retired and current NFL players (n = 161) were recruited in a longitudinal study starting in 2009 with ongoing interval follow up. A healthy control group (n = 124) was separately recruited for comparison. Assessments included medical examinations, neuropsychological tests, and perfusion neuroimaging with single photon emission computed tomography (SPECT). Perfusion estimates of each scan were quantified using a standard atlas. We hypothesized that hypoperfusion particularly in the orbital frontal, anterior cingulate, anterior temporal, hippocampal, amygdala, insular, caudate, superior/mid occipital, and cerebellar sub-regions alone would reliably separate controls from NFL players. Cerebral perfusion differences were calculated using a one-way ANOVA and diagnostic separation was determined with discriminant and automatic linear regression predictive models., Results: NFL players showed lower cerebral perfusion on average (p < 0.01) in 36 brain regions. The discriminant analysis subsequently distinguished NFL players from controls with 90% sensitivity, 86% specificity, and 94% accuracy (95% CI 95-99). Automatic linear modeling achieved similar results. Inclusion of age and clinical co-morbidities did not improve diagnostic classification., Conclusion: Specific brain regions commonly damaged in traumatic brain injury show abnormally low perfusion on SPECT in professional NFL players. These same regions alone can distinguish this group from healthy subjects with high diagnostic accuracy. This study carries implications for the neurological safety of NFL players.

Since it was first used to image the brain in 1976, positron emission tomography (PET) has been utilized in a wide range of neurologic and psychiatric applications. From cerebral metabolism to receptor concentration, various PET imaging techniques involving a host of radiopharmaceuticals have provided insight into countless facets of both the normal and diseased brain. Although the majority of these radiopharmaceuticals are still limited to the realm of research, one PET ligand in particular has gained widespread clinical use: (18)F-fluorodeoxyglucose, a radiolabeled analog of glucose, has become an exceedingly prevalent clinical tool for the measurement of metabolism in organs throughout the body, including the brain. In recent years, a number of novel PET ligands have also made it through the US Food and Drug Administration approval process and been used clinically. However, gaining approval is by no means the only challenge facing these radiopharmaceuticals. Traversing the blood-brain barrier is a formidable obstacle in drug delivery, and accurately modeling tracer kinetics and correcting for the partial-volume effect are among the difficult tasks that remain once the ligand reaches its intended target. Even so, the use of PET imaging in neurology and psychiatry can be expected to expand in the coming years as novel radiopharmaceuticals continue to be developed., (© 2016 Elsevier B.V. All rights reserved.)

PTSD and TBI are two common conditions in veteran populations that can be difficult to distinguish clinically. The default mode network (DMN) is abnormal in a multitude of neurological and psychiatric disorders. We hypothesize that brain perfusion SPECT can be applied to diagnostically separate PTSD from TBI reliably in a veteran cohort using DMN regions. A group of 196 veterans (36 with PTSD, 115 with TBI, 45 with PTSD/TBI) were selected from a large multi-site population cohort of individuals with psychiatric disease. Inclusion criteria were peacetime or wartime veterans regardless of branch of service and included those for whom the traumatic brain injury was not service related. SPECT imaging was performed on this group both at rest and during a concentration task. These measures, as well as the baseline-concentration difference, were then inputted from DMN regions into separate binary logistic regression models controlling for age, gender, race, clinic site, co-morbid psychiatric diseases, TBI severity, whether or not the TBI was service related, and branch of armed service. Predicted probabilities were then inputted into a receiver operating characteristic analysis to compute sensitivity, specificity, and accuracy. Compared to PSTD, persons with TBI were older, male, and had higher rates of bipolar and major depressive disorder (p < 0.05). Baseline quantitative regions with SPECT separated PTSD from TBI in the veterans with 92 % sensitivity, 85 % specificity, and 94 % accuracy. With concentration scans, there was 85 % sensitivity, 83 % specificity and 89 % accuracy. Baseline-concentration (the difference metric between the two scans) scans were 85 % sensitivity, 80 % specificity, and 87 % accuracy. In separating TBI from PTSD/TBI visual readings of baseline scans had 85 % sensitivity, 81 % specificity, and 83 % accuracy. Concentration scans had 80 % sensitivity, 65 % specificity, and 79 % accuracy. Baseline-concentration scans had 82 % sensitivity, 69 % specificity, and 81 % accuracy. For separating PTSD from PTSD/TBI baseline scans had 87 % sensitivity, 83 % specificity, and 92 % accuracy. Concentration scans had 91 % sensitivity, 76 % specificity, and 88 % accuracy. Baseline-concentration scans had 84 % sensitivity, 64 % specificity, and 85 % accuracy. This study demonstrates the ability to separate PTSD and TBI from each other in a veteran population using functional neuroimaging.

Importance: Amyloid-β positron emission tomography (PET) imaging allows in vivo detection of fibrillar plaques, a core neuropathological feature of Alzheimer disease (AD). Its diagnostic utility is still unclear because amyloid plaques also occur in patients with non-AD dementia., Objective: To use individual participant data meta-analysis to estimate the prevalence of amyloid positivity on PET in a wide variety of dementia syndromes., Data Sources: The MEDLINE and Web of Science databases were searched from January 2004 to April 2015 for amyloid PET studies., Study Selection: Case reports and studies on neurological or psychiatric diseases other than dementia were excluded. Corresponding authors of eligible cohorts were invited to provide individual participant data., Data Extraction and Synthesis: Data were provided for 1359 participants with clinically diagnosed AD and 538 participants with non-AD dementia. The reference groups were 1849 healthy control participants (based on amyloid PET) and an independent sample of 1369 AD participants (based on autopsy)., Main Outcomes and Measures: Estimated prevalence of positive amyloid PET scans according to diagnosis, age, and apolipoprotein E (APOE) ε4 status, using the generalized estimating equations method., Results: The likelihood of amyloid positivity was associated with age and APOE ε4 status. In AD dementia, the prevalence of amyloid positivity decreased from age 50 to 90 years in APOE ε4 noncarriers (86% [95% CI, 73%-94%] at 50 years to 68% [95% CI, 57%-77%] at 90 years; n = 377) and to a lesser degree in APOE ε4 carriers (97% [95% CI, 92%-99%] at 50 years to 90% [95% CI, 83%-94%] at 90 years; n = 593; P < .01). Similar associations of age and APOE ε4 with amyloid positivity were observed in participants with AD dementia at autopsy. In most non-AD dementias, amyloid positivity increased with both age (from 60 to 80 years) and APOE ε4 carriership (dementia with Lewy bodies: carriers [n = 16], 63% [95% CI, 48%-80%] at 60 years to 83% [95% CI, 67%-92%] at 80 years; noncarriers [n = 18], 29% [95% CI, 15%-50%] at 60 years to 54% [95% CI, 30%-77%] at 80 years; frontotemporal dementia: carriers [n = 48], 19% [95% CI, 12%-28%] at 60 years to 43% [95% CI, 35%-50%] at 80 years; noncarriers [n = 160], 5% [95% CI, 3%-8%] at 60 years to 14% [95% CI, 11%-18%] at 80 years; vascular dementia: carriers [n = 30], 25% [95% CI, 9%-52%] at 60 years to 64% [95% CI, 49%-77%] at 80 years; noncarriers [n = 77], 7% [95% CI, 3%-18%] at 60 years to 29% [95% CI, 17%-43%] at 80 years., Conclusions and Relevance: Among participants with dementia, the prevalence of amyloid positivity was associated with clinical diagnosis, age, and APOE genotype. These findings indicate the potential clinical utility of amyloid imaging for differential diagnosis in early-onset dementia and to support the clinical diagnosis of participants with AD dementia and noncarrier APOE ε4 status who are older than 70 years.

Importance: Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies., Objective: To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI)., Data Sources: Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators., Study Selection: Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity., Data Extraction and Synthesis: Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies., Main Outcomes and Measures: Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations., Results: The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOE ε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality., Conclusions and Relevance: Among persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, APOE genotype, and presence of cognitive impairment. These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia.

Several studies have reported low brain serotonin transporter (SERT) binding in individuals with major depression. We hypothesized that the SERT standardized uptake ratio (SUR) values using [(123) I]-ADAM single photon emission computed tomography would increase in depressed subjects who responded to cognitive behavior therapy (CBT) compared to CBT nonresponders. [(123) I]-ADAM scans were acquired before and after 12 weeks of CBT from 20 depressed subjects and on two occasions 12 weeks apart from 10 nondepressed, healthy volunteers. The primary outcome measure was change over time in SUR values in the midbrain, medial temporal lobe, and basal ganglia regions. Depressed subjects demonstrated low pretreatment mean SUR values that significantly increased over time in the midbrain (P = .011), right medial temporal lobe (P = .008), and left medial temporal lobe (P = .000) regions. Treatment responders showed a significant increase over time in SUR values in left medial temporal lobe (P = .029) and right medial temporal lobe (P = .007) regions. Partial and nonresponder subjects also showed a significant increase over time in SUR values in the left medial temporal region (P = .040) (vs. healthy volunteers), but to a lesser degree. The findings suggest that low pretreatment SERT binding may increase over time in some depressed individuals who experience symptom improvement., (Copyright © 2013 by the American Society of Neuroimaging.)

This study employed functional magnetic resonance imaging to evaluate changes in cerebral blood flow (CBF) associated with the Mindfulness-based Art Therapy (MBAT) programme and correlate such changes to stress and anxiety in women with breast cancer. Eighteen breast cancer patients were randomized to the MBAT or education control group. The patients received the diagnosis of breast cancer between 6 months and 3 years prior to enrollment and were not in active treatment. The age of participants ranged from 52 to 77 years. A voxel-based analysis was performed to assess differences at rest, during meditation and during a stress task. The anxiety sub-scale of the Symptoms Checklist-90-Revised was compared with changes in resting CBF before and after the programmes. Subjects in the MBAT arm demonstrated significant increases in CBF at rest and during meditation in multiple limbic regions, including the left insula, right amygdala, right hippocampus and bilateral caudate. Patients in the MBAT programme also had a significant correlation between increased CBF in the left caudate and decreased anxiety scores. In the MBAT group, responses to a stressful cue resulted in reduced activation of the posterior cingulate. The results demonstrate that the MBAT programme was associated with significant changes in CBF, which correlated with decreased anxiety over an 8-week period., (Copyright © 2012 John Wiley & Sons, Ltd.)

We examined midbrain, medial temporal lobe, and basal ganglia serotonin transporter (SERT) distribution volume ratio (DVR) values in subjects with major depressive disorder versus healthy volunteers using a selective SERT radioligand and single photon emission computed tomography (SPECT). We hypothesized that the DVR value for SERT binding would be lower in depressed versus non-depressed subjects. [(123)I]-ADAM SPECT scans were acquired from 20 drug free, depressed subjects and 20 drug-free depressed subjects and 10 drug-free healthy volunteers. The primary outcome measure was the DVR value for [(123)I]-ADAM uptake in the midbrain, medial temporal lobe, and basal ganglia regions. Depressed subjects demonstrated significantly lower DVR values in the midbrain, right and left medial temporal lobe, and right and left basal ganglia. There was significant probability that lower DVR values could distinguish between depressed and non-depressed subjects in the midbrain, medial temporal lobe, and the right and left basal ganglia. These findings confirm prior observations of lower SERT binding in depression, and suggest that low SERT binding may represent a putative biomarker of depression. Future studies are needed to confirm these observations., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Our objective was to ascertain in a prospective case series how often brain single photon emission computed tomography (SPECT) neuroimaging adds relevant information for diagnosis and/or treatment beyond current standard assessment tools in complex psychiatric cases. Charts of 109 consecutively evaluated outpatients from four psychiatrics clinics that routinely utilize SPECT imaging for complex cases were analyzed in two stages. In stage one, psychiatrists reviewed detailed clinical histories, mental status exams, and the structured clinical interview for DSM-IV, but not the results of SPECT studies, assigned a diagnosis based on DSM-IV criteria, and then developed a comprehensive treatment plan. In stage two, evaluators were given access to the SPECT studies for each patient. The addition of SPECT modified the diagnosis or treatment plan in 78.9% (n=86; rated level 2 or 3 change) of cases. The most clinically significant changes were undetected brain trauma (22.9%), toxicity patterns (22.9%) and the need for a structural imaging study (9.2%). Specific functional abnormalities were seen as follows that potentially could impact treatment: temporal lobe dysfunction (66.1%) and prefrontal hypoperfusion (47.7%). SPECT has the potential to add clinically meaningful information to enhance patient care beyond current assessment tools in complex or treatment resistant cases.

The authors recruited 100 active and former National Football League players, representing 27 teams and all positions. Players underwent a clinical history, brain SPECT imaging, qEEG, and multiple neuropsychological measures, including MicroCog. Relative to a healthy-comparison group, players showed global decreased perfusion, especially in the prefrontal, temporal, parietal, and occipital lobes, and cerebellar regions. Quantitative EEG findings were consistent, showing elevated slow waves in the frontal and temporal regions. Significant decreases from normal values were found in most neuropsychological tests. This is the first large-scale brain-imaging study to demonstrate significant differences consistent with a chronic brain trauma pattern in professional football players.

Evidence points to the endogenous opioid system, and the mu-opioid receptor (MOR) in particular, in mediating the rewarding effects of drugs of abuse, including nicotine. A single nucleotide polymorphism (SNP) in the human MOR gene (OPRM1 A118G) has been shown to alter receptor protein level in preclinical models and smoking behavior in humans. To clarify the underlying mechanisms for these associations, we conducted an in vivo investigation of the effects of OPRM1 A118G genotype on MOR binding potential (BP(ND) or receptor availability). Twenty-two smokers prescreened for genotype (12 A/A, 10 */G) completed two [(11)C]carfentanil positron emission tomography (PET) imaging sessions following overnight abstinence and exposure to a nicotine-containing cigarette and a denicotinized cigarette. Independent of session, smokers homozygous for the wild-type OPRM1 A allele exhibited significantly higher levels of MOR BP(ND) than smokers carrying the G allele in bilateral amygdala, left thalamus, and left anterior cingulate cortex. Among G allele carriers, the extent of subjective reward difference (denicotinized versus nicotine cigarette) was associated significantly with MOR BP(ND) difference in right amygdala, caudate, anterior cingulate cortex, and thalamus. Future translational investigations can elucidate the role of MORs in nicotine addiction, which may lead to development of novel therapeutics.

Our goal in this study was to advance the understanding of the neural pathways of meditation by addressing the cerebral blood flow (CBF) responses associated with two different meditation practices performed by the same individuals and how such changes related to the "stress" circuits in the brain. Ten experienced meditators performed two types of meditation, a "focused-based" practice and a "breath-based" practice. Subjects were scanned using perfusion functional magnetic resonance imaging (fMRI) during a baseline state, both meditation states, and a post meditation baseline state. Using general linear model, we found that the frontal regions, anterior cingulate, limbic system and parietal lobes were affected during meditation and that there were different patterns of CBF between the two meditation states. We observed strong correlations between depth of meditation and neural activity in the left inferior forebrain areas including the insula, inferior frontal cortex, and temporal pole. There were persistent changes in the left anterior insula and the precentral gyrus even after meditation was stopped. This study revealed changes in the brain during two different meditation practices in the same individuals and that these changes correlated with the subjective experiences of the practitioners., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

We have studied a number of long-term meditators in previous studies. The purpose of this study was to determine if there are differences in baseline brain function of experienced meditators compared to non-meditators. All subjects were recruited as part of an ongoing study of different meditation practices. We evaluated 12 advanced meditators and 14 non-meditators with cerebral blood flow (CBF) SPECT imaging at rest. Images were analyzed with both region of interest and statistical parametric mapping. The CBF of long-term meditators was significantly higher (p<.05) compared to non-meditators in the prefrontal cortex, parietal cortex, thalamus, putamen, caudate, and midbrain. There was also a significant difference in the thalamic laterality with long-term meditators having greater asymmetry. The observed changes associated with long-term meditation appear in structures that underlie the attention network and also those that relate to emotion and autonomic function., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: To examine changes in brain physiology during a chanting meditation practice using cerebral blood flow single-photon emission computed tomography., Methods: Single-photon emission computed tomography scans were acquired in 11 healthy individuals during either a resting state or meditation practice randomly performed on two separate days. Statistical parametric mapping analyses were conducted to identify significant changes in regional cerebral blood flow (rCBF) between the two conditions., Results: When the meditation state was compared with the baseline condition, significant rCBF increases were observed in the right temporal lobe and posterior cingulate gyrus, and significant rCBF decreases were observed in the left parietotemporal and occipital gyri., Conclusion: The results offer evidence that this form of meditation practice is associated with changes in brain function in a way that is consistent with earlier studies of related types of meditation as well as with the positive clinical outcomes anecdotally reported by its users.

Objectives: Experienced practitioners of yoga have been shown to alter brain function, but this case series measured cerebral blood flow before and after a 12-week training program in Iyengar yoga (IY) for naïve subjects., Methods: On the first day, each of the 4 subjects listened to the teacher speaking on the history and background of the yoga program while they were injected with 250 MBq of (99m)Tc-bicisate and received a single photon emission computed tomography scan (pre-program baseline). Subjects then had their first IY training and were injected and scanned with 925 MBq bicisate while they did their first meditation (pre-program meditation). Subjects then underwent a 12-week training program in IY and then underwent the same imaging protocol with a postprogram baseline and postprogram meditation scan. Baseline and meditation scans, before and after training, were compared using paired t tests., Results: There were significant decreases (p < 0.05) between the pre- and postprogram baseline scans in the right amygdala, dorsal medial cortex, and sensorimotor area. There was a significant difference (p < 0.05) in the pre- and postprogram percentage change (i.e., activation) in the right dorsal medial frontal lobe, prefrontal cortex, and right sensorimotor cortex., Conclusions: These initial findings suggest the brain experiences a "training effect" after 12 weeks of IY training.

Head trauma requires several different neuroimaging modalities for adequate evaluation and determination of treatment. This article considers the importance of anatomical and functional imaging modalities in the initial evaluation, treatment planning, and long-term management of patients with head injury. These modalities include computed tomography, magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography. Each modality offers specific advantages and potential disadvantages. However, it is important to understand the capabilities of each modality, and how and when each one might provide the most valuable information as one evaluates such patients.

Night eating syndrome (NES) represents a delay in the circadian pattern of food intake, manifested by evening hyperphagia and/or nocturnal awakenings accompanied by ingestions of food. A neurobiological marker of NES has been implicated with the recently discovered therapeutic response to the selective serotonin reuptake inhibitor (SSRI) sertraline. This pilot SPECT (single photon emission computed tomography) study compared the serotonin transporter (SERT) uptake ratios of night eaters with those of healthy controls. Six night eaters underwent SPECT imaging using the radiopharmaceutical (123)I-ADAM. Uptake, compared with that of the cerebellum, was obtained for the midbrain, basal ganglia, and temporal lobes; uptake ratios in night eaters were compared with those of six healthy controls. Night eaters had significantly greater SERT uptake ratios in the midbrain than healthy controls. These findings, in conjunction with the therapeutic response of NES to sertraline, indicate that the serotonin system is involved in the pathophysiology of NES.

Background: Traumatic memory is a key symptom in psychological trauma victims and may remain vivid for several years. Psychotherapy has shown that neither the psychopathological signs of trauma nor the expression of traumatic memories are static over time. However, few studies have investigated the neural substrates of psychotherapy-related symptom changes., Method: We studied 16 subthreshold post-traumatic stress disorder (PTSD) subjects by using a script-driven symptom provocation paradigm adapted for single photon emission computed tomography (SPECT) that was read aloud during traumatic memory retrieval both before and after exposure-based and cognitive restructuring therapy. Their neural activity levels were compared with a control group comprising 11 waiting-list subthreshold PTSD patients, who were age- and profile-matched with the psychotherapy group., Results: Significantly higher activity was observed in the parietal lobes, left hippocampus, thalamus and left prefrontal cortex during memory retrieval after psychotherapy. Positive correlations were found between activity changes in the left prefrontal cortex and left thalamus, and also between the left prefrontal cortex and left parietal lobe., Conclusions: Neural mechanisms involved in subthreshold PTSD may share neural similarities with those underlying the fragmented and non-verbal nature of traumatic memories in full PTSD. Moreover, psychotherapy may influence the development of a narrative pattern overlaying the declarative memory neural substrates.

In recent years, investigators have made significant progress in documenting brain structure and function as it relates to aging by using positron emission tomography, conventional magnetic resonance (MR) imaging, advanced MR techniques, and functional MR imaging. This review summarizes the latest advances in understanding physiologic maturation and aging as detected by these neuroimaging modalities. We also present our experience with MR volumetric and positron emission tomography analysis in separate cohorts of healthy subjects in the pediatric and adult age groups respectively. Our results are consistent with previous studies and include the following: total brain volume was found to increase with age (up to 20 years of age). Whole brain metabolism and frontal lobe metabolism both decrease significantly with age (38% and 42%, respectively), whereas cerebellar metabolism does not show a significant decline with age. Defining normal alterations in brain function and structure allows early detection of disorders such as Alzheimer's and Parkinson's diseases, which are commonly associated with normal aging.

Glossolalia (or "speaking in tongues") is an unusual mental state that has great personal and religious meaning. Glossolalia is experienced as a normal and expected behavior in religious prayer groups in which the individual appears to be speaking in an incomprehensible language. This is the first functional neuroimaging study to demonstrate changes in cerebral activity during glossolalia. The frontal lobes, parietal lobes, and left caudate were most affected.

A novel approach for concurrent measurement of regional cerebral blood flow (CBF) and regional cerebral metabolic rate for glucose consumption (CMRGlc) in humans is proposed and validated in normal subjects during visual stimulation. 18F-labeled fluorodeoxyglucose was administered during the measurement of CBF by continuous arterial spin labeled magnetic resonance imaging (MRI). Subsequent positron emission tomographic (PET) scanning demonstrated the distribution of labeled deoxyglucose during the MRI acquisition. An excellent concordance between regional CBF and regional CMRGlc during visual stimulation was found, consistent with previously published PET findings. Although initially validated using a brief, non-quantitative protocol, this approach can provide quantitative CBF and CMRGlc, with a broad range of potential applications in functional physiology and pathophysiology.

Objective: Authors investigated the association between estrogen replacement therapy (ERT) and dopamine transporter (DAT) availability in women., Methods: Thirteen postmenopausal women were administered ERT and underwent neuroimaging, using single-photon emission computed tomography (SPECT) and [99mTc]TRODAT-1, a radioligand that binds DAT. In this 6-week pilot study, subjects underwent SPECT before ERT, after 4 weeks of 0.625 mg/day of conjugated estrogens (CEE), and after an additional 2 weeks of 0.625 mg/day CEE plus 10 mg/day of medroxyprogesterone acetate. Specific uptake values (SUVs) of [99mTc]TRODAT-1 were calculated for the caudate and putamen., Results: When compared with baseline values, [99mTc]TRODAT-1 binding demonstrated a modest, but statistically significant, increase in the left anterior putamen after 4 weeks of CEE. After the 6-week ERT intervention, both the left and right anterior putamen demonstrated an increase in SUVs., Conclusion: Short-term administration of ERT in postmenopausal women is associated with a modest increase in DAT in the putamen. These findings may further the understanding of how ERT is associated with improvement in Parkinson's disease and late-onset schizophrenia.

Cerebral blood flow and metabolism may be uncoupled in the early phases after stroke onset. Prior reports of bilateral thalamic stroke have described subsequent coupling of blood flow and metabolism during the chronic stage. We chronicled the evolving relationship of blood flow and metabolism with concomitant single photon emission CT and positron emission tomography from the subacute to chronic phase following bilateral thalamic infarction.

Purpose: Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) may be used to establish a diagnosis of encephalitis, yet prior descriptions are mainly limited to small case reports. We explore the role of FDG-PET in the diagnostic evaluation of encephalitis., Methods: Brain FDG-PET was acquired in a consecutive case series of 10 cases of suspected encephalitis over a 5-year-period. Cases with positive Lyme serology were excluded. Two expert reviewers graded the FDG-PET studies in blinded fashion with respect to the clinical history. Retrospective review of the clinical history and examination, laboratory findings, electroencephalogram (EEG), and magnetic resonance imaging (MRI) studies was performed. A diagnosis of encephalitis was based on a combination of the clinical and diagnostic examination findings in each case., Results: Encephalitis was diagnosed in 6 of 10 cases. FDG-PET hypermetabolism was demonstrated in 5 cases of encephalitis, most frequently involving the medial temporal lobes. Multifocal hypometabolism was noted in at least 2 regions in all 6 cases of encephalitis, with at least 4 regions of hypometabolism noted in 5 of 6 cases. Nonencephalitis cases revealed hypermetabolism in only 1 of 4 cases, ascribed to status epilepticus. Hypometabolism was evident in all nonencephalitis cases., Conclusion: Encephalitis frequently manifests as FDG-PET hypermetabolism, but focal hypometabolism can also be observed. Seizure activity must be excluded as a possible cause of hypermetabolism in patients suspected of having encephalitis. Because other conditions that can cause hypometabolism may mimic encephalitis clinically, FDG-PET is more likely to serve as an adjunct to lumbar puncture, EEG, and clinical findings rather than a primary diagnostic tool in the management of patients suspected of having encephalitis.

Unlabelled: 2-((2-((Dimethylamino)methyl)phenyl)thio)-5-(123)I-iodophenylamine ((123)I-ADAM) is a new radiopharmaceutical that selectively binds the central nervous system serotonin transporters. The purpose of this study was to measure its whole-body biokinetics and estimate its radiation dosimetry in healthy human volunteers. The study was conducted within a regulatory framework that required its pharmacologic safety to be assessed simultaneously., Methods: The sample included 7 subjects ranging in age from 22 to 54 y old. An average of 12.7 whole-body scans were acquired sequentially on a dual-head camera for up to 50 h after the intravenous administration of 185 MBq (5 mCi) (123)I-ADAM. The fraction of the administered dose in 13 regions of interest (ROIs) was quantified from the attenuation-corrected geometric mean counts in conjugate views. Multiexponential functions were iteratively fit to each time-activity curve using a nonlinear, least-squares regression algorithm. These curves were numerically integrated to yield source organ residence times. Gender-specific radiation doses were then estimated with the MIRD technique. SPECT brain scans obtained 3 h after injection were evaluated using an ROI analysis to determine the range of values for the region to cerebellum., Results: There were no pharmacologic effects of the radiotracer on any of the subjects, including no change in heart rate, blood pressure, or laboratory results. Early planar images showed differentially increased activity in the lungs. SPECT images demonstrated that the radiopharmaceutical localized in the midbrain in a distribution that is consistent with selective transporter binding. The dose-limiting organ in both men and women was the distal colon, which received an average of 0.12 mGy/MBq (0.43 rad/mCi) (range, 0.098-0.15 mGy/MBq). The effective dose equivalent and effective dose for (123)I-ADAM were 0.037 +/- 0.003 mSv/MBq and 0.036 +/- 0.003 mSv/MBq, respectively. The mean adult male value of effective dose for (123)I-ADAM is similar in magnitude to that of (111)In-diethylenetriaminepentaacetic acid (0.035 mGy/MBq), half that of (111)In-pentetreotide (0.81 mGy/MBq), and approximately twice that of (123)I-inosine 5'-monophosphate (0.018 mGy/MBq). The differences in results between this study and a previous publication are most likely due to several factors, the most prominent being this dataset used attenuation correction of the scintigraphic data. Region-to-cerebellum ratios for the brain SPECT scans were 1.95 +/- 0.13 for the midbrain, 1.27 +/- 0.10 for the medial temporal regions, and 1.11 +/- 0.07 for the striatum., Conclusion: (123)I-ADAM may be a safe and effective radiotracer for imaging serotonin transporters in the brain and the body.

Meditative practices typically require several coordinated cognitive activities. This study measured changes in cerebral blood flow during "verbal" based meditation by Franciscan nuns involving the internal repetition of a particular phrase. These results are compared with those we previously described in eight Buddhist meditators who use a type of "visualization" technique. Three experienced practitioners of verbal meditation were injected via i.v. at rest with 260 MBq of Tc-99m HMPAO and scanned 30 min. later on a triple head SPECT camera for 45 min. Following the baseline scan, subjects meditated for approximately 40 min. at which time they were injected with 925 MBq of HMPAO while they continued to meditate for 10 min. more (total of 50 min. of meditation). The injection during meditation was designed not to disturb practice. Subjects were scanned 20 min. later for 30 min. Counts were obtained for regions of interest for major brain structures and normalized to whole-brain blood flow. Compared to baseline, mean verbal meditation scans showed increased blood flow in the prefrontal cortex (7.1%), inferior parietal lobes (6.8%), and inferior frontal lobes (9.0%). There was a strong inverse correlation between the blood flow, change in the prefrontal cortex and in the ipsilateral superior parietal lobe (p<.01). This study on a limited number of subjects demonstrated the feasibility of studying different types of meditation with neuroimaging techniques, suggested that several coordinated cognitive processes occur during meditation, and also raised important methodological issues.

Objective: Studies of laboratory animals have shown that administration of antidepressants of all pharmacological classes produces changes in dopamine transporter binding affinity. These observations suggest that dopamine transporter function may play a critical role in the pathophysiology of depression. The present study was an examination of the availability of brain dopamine transporter sites in patients with major depression and in healthy comparison subjects., Method: Single photon emission computed tomographic (SPECT) brain scans were acquired for 15 drug-free depressed patients and 46 age- and gender-matched healthy comparison subjects by using [(99m)Tc]TRODAT-1, a selective dopamine transporter imaging agent. Specific regions of interest in the basal ganglia and supratentorial areas of the brain were examined. Specific uptake values of dopamine transporter [(99m)Tc]TRODAT-1 binding affinity were calculated from the SPECT scan data, and the values for the patients and healthy subjects were compared., Results: The specific uptake values of [(99m)Tc]TRODAT-1 binding were significantly higher in the right anterior putamen (23%), right posterior putamen (36%), left posterior putamen (18%), and left caudate nucleus (12%) of the patients than in the comparison subjects. These differences persisted when the data were further analyzed according to gender and age., Conclusions: Dopamine transporter affinity may be higher than normal in the basal ganglia of depressed patients. These findings suggest that dopamine function may be altered in depression and may also be a mechanism of antidepressant activity.

Purpose: This study was designed to validate a simple scoring system for evaluating fluorodeoxyglucose (FDG) positron emission tomographic (PET) scans that can be used routinely in patients undergoing the clinical assessment of cognitive impairment., Methods: The FDG-PET scans of 106 patients with cognitive impairment (65 with Alzheimer disease, 16 with frontal lobe dementia, and 25 atypical cases) were acquired using the PENN-PET scanner 40 minutes after the intravenous administration of 8 mCi FDG. Metabolic activity in various anatomic structures of the brain was scored using the following qualitative scale: 4 = normal; 3 = mildly decreased; 2 = moderately decreased; 1 = severely decreased; and 0 = no activity. Regions of interest were also placed over these regions to obtain a quantitative value. Two distinct scores were obtained. Values for visual and sensorimotor cortices, thalami, basal ganglia, and cerebellum comprised score I. Score II consisted of the values for the frontal, temporal, and parietal cortices. The qualitative metabolic imaging severity rating scale (MISRS) was compared with a quantitative MISRS (obtained from the region-of-interest analysis of the same structures). The MISRS was then compared with the results from the Mini-Mental Status Examination (MMSE) and the Dementia Severity Rating Score (DSRS)., Results: In all patients, the qualitative MISRS scores correlated significantly with the quantitative MISRS (r = 0.73, P < 0.0001). In all patients with cognitive impairment, the qualitative and quantitative MISRS scores correlated significantly with the DSRS and the MMSE (P < 0.001). In patients with Alzheimer disease, the qualitative and quantitative MISRS significantly correlated with the DSRS and MMSE., Conclusion: A simple and practical rating scale can be used to assess the severity of cognitive impairment in patients with different types of dementing illnesses.

One of the most important issues in evaluating functional brain scans for research or clinical purposes is to be able to identify normal variants. Determining the baseline "normal" state of the brain is not easy to characterize since many normal brain functions and mental processes affect brain activity. This article reviews issues pertaining to the technical and neurophysiological aspects of functional brain imaging that might alter "normal" activity and will also consider how normal brain activity changes throughout the lifespan.

Functional brain imaging using 18F fluorodeoxyglucose (FDG) and positron emission tomography (PET) has greatly enhanced our understanding of brain function both in normal conditions as well as in a wide variety of neuropsychiatric disorders. We review the uses of FDG PET in the diagnosis, management, and follow-up of patients with neuropsychiatric disorders. This article will also explore what FDG-PET imaging has revealed in these neuropsychiatric disorders and how these findings relate to both research and clinical applications.

This article reviews the neuroscientific understanding of the self and personal identity, focusing on various elements of inclusivity and exclusivity as well as engaging religious and spiritual perspectives. We will also consider how the identity is comprised of biological, social, and ideological or spiritual aspects, and how they are interconnected. We will consider how the brain helps us to construct and maintain our representation of the self and what happens when we have self‐transcendent experiences. Such an evaluation will have implications for understanding the intersection between consciousness and the self. This information will be helpful from both the psychological and spiritual perspective for understanding human identity. [ABSTRACT FROM AUTHOR]

This article reviews and synthesizes the current data on the relationship between the brain and religion and spirituality, with regard to aging and neurodegenerative diseases. Specifically, we consider how religious and spiritual beliefs, attitudes, and practices might be affected by the aging process on the brain, particularly when neurodegenerative diseases occur. Various practices such as meditation or prayer also are associated with brain processes and such a relationship could have clinical implications for the use of these practices to help the elderly improve anxiety, depression, or cognition. Finally, we consider potential negative relationships such as religious struggle that can be part of the relationship between the brain and religious or spiritual beliefs as people age. In the end, it is hoped that this neurotheological approach, combining an understanding of brain processes with religious and spiritual phenomena, can be useful in deepening our knowledge regarding the impact of aging and neurogenerative diseases on brain function, and concomitantly on religiousness and spirituality in the elderly population. [ABSTRACT FROM AUTHOR]

This article reviews the most recent information and data regarding brain processes associated with altered states of consciousness. It takes a neurotheological approach, seeking to blend what is known about these states, particularly as they relate to religious and spiritual experiences, in terms of brain processes and subjective elements of the experiences. The overall goal is to provide a comprehensive model that incorporates multiple brain areas including cortical, limbic, and subcortical structures, as well as considers the various neurotransmitters that might be involved. It is the hope that this framework provides a starting point for future investigations into the detailed neurophysiological and phenomenal aspects of altered states of consciousness. [ABSTRACT FROM AUTHOR]

A neurotheological approach suggests an analysis of spiritual awakening experiences by combining phenomenological data with neuroscience. This paper presents a synthesis combining information on the thoughts, feelings, and experiences associated with spiritual awakening experiences and neurophysiological data, primarily from neuroimaging studies, to help assess which brain structures might be associated with these experiences. Brain structures involved with emotions correlate with emotional responses while areas of the brain associated with the sense of self appear to correlate with the key feature of these experiences in which an individual loses the sense of self and feels intimately connected with God, universal consciousness, or the universe. This paper also seeks to address the assumption whether awakened states as described in popular spirituality are similar or different compared to spiritual enlightenment as described in Eastern spiritual traditions. Thus, the implications of such a neurotheological analysis are also considered. [ABSTRACT FROM AUTHOR]